Emerging hormonal agents for the treatment of prostate cancer

ABSTRACT

Introduction

Prostate cancer is the most common solid organ malignancy in men in the United States. Until recently, treatment options for men with metastatic disease were limited and patients faced poor outcomes with minimal alternatives. The landscape of prostate cancer treatment has transformed and taken shape over the last 20 years with novel hormonal and non-hormonal therapeutics that have demonstrated significant improvement in survival. However, patients with advanced disease still face imminent progression on hormone blockade therapy.

Areas covered

There is a significant market opportunity to devise novel, more potent agents for patients with hormone-resistant disease. Here we review the existing treatment options in men with advanced prostate cancer, the market opportunity within this field, goals of current research, and the novel agents under investigation, including androgen receptor degraders, testosterone synthesis pathway inhibitors, DNA-binding domain and N-terminal domain antagonists, and the combination of hormonal and non-hormonal agents.

Expert opinion

Combination therapy regimens and novel agents targeting alternative binding domains of the androgen receptor are of great interest, as they may overcome resistance mechanisms and hold promise as the future of advanced prostate cancer treatment.

KEYWORDS:

• Testosterone
• androgen receptor
• emerging therapies

Declaration of interest

GV Raj holds multiple issued and pending patents, which has been licensed to EtiraRx. GV Raj serves or has served in an advisory role to Bayer, Johnson and Johnson, Myovant, EtiraRx, Amgen, Pfizer and Astellas. GV Raj has or has had grant support from Bayer, EtiraRx and Johnson and Johnson. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they conduct trials of PSMA PET imaging and therapeutics and have research collaborations with Invicro and Siemens. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was made possible by funding to GV R from the Simmons Cancer Center at UT Southwestern for the Prostate Cancer Program, the Mimi and John Cole Prostate Cancer Fund, the Wilson Foundation and the Department of Defense Grants W81XWH-17-1-0674, W81XWH-19-1-0363, and W81XWH-21-1-0687.